Large-scale protein interaction networks have been determined experimentally for several organisms, and computational analysis of these networks provides new opportunities to uncover protein functions and pathways. At the same time, despite improvements in high-throughput technologies, it is still not feasible in the near future to apply them to all sequenced genomes. Thus, for the vast majority of sequenced genomes, only a small fraction of known protein interactions have been experimentally determined, and novel computational approaches provide a promising, alternative means for building large, high- confidence interaction maps. The broad, long-term goal of this research is to build a comprehensive research program for understanding protein interactions, by developing algorithms for the complementary problems of analyzing and predicting protein interaction maps. Our specific aims are: (1) To develop algorithms that exploit the topology of whole-genome protein interaction maps and the relationships between protein functions, in order to make novel predictions about a protein's biological process. (2) To build a system for interrogating protein interaction networks using "templates" specifying common patterns of interactions or pathways, in order to help uncover novel instances. (3) To develop a general structural bioinformatics approach for leveraging properties of specific protein interaction interfaces, and to apply this approach in order to help predict Cys2HiS2 zinc finger protein-DNA interactions at the genomic scale. Taken together, we hope that the proposed tools will significantly advance the state-of-the-art in computational approaches for characterizing proteins within the context of their cellular interactions, pathways and networks. All software and predictions will be made publicly available via the internet.